TDO2

tryptophan 2,3-dioxygenase

Basic information

Region (hg38): 4:155854738-155920406

Links

ENSG00000151790 ∙ NCBI:6999 ∙ OMIM:191070 ∙ HGNC:11708 ∙ Uniprot:P48775 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial hypertryptophanemia (Supportive), mode of inheritance: AR
• familial hypertryptophanemia (Limited), mode of inheritance: Unknown
• familial hypertryptophanemia (Limited), mode of inheritance: AR
• familial hypertryptophanemia (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypertryptophanemia	AD	General	The clinical relevance of the condition is unclear	Biochemical	28285122

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TDO2 gene.

• not_specified (47 variants)
• TDO2-related_disorder (3 variants)
• not_provided (2 variants)
• Familial_hypertryptophanemia (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TDO2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005651.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	1	3
missense			49	1	1	51
nonsense						0
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)			1			1
Total	0	0	51	3	2

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TDO2	protein_coding	protein_coding	ENST00000536354	12	65669

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125653	1	94	125748	0.000378

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.221	210	201	1.04	0.00000987	2651
Missense in Polyphen		91	72.899	1.2483		952
Synonymous	-0.303	77	73.7	1.04	0.00000357	718
Loss of Function	1.40	19	26.8	0.708	0.00000156	316

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000689	0.000689
Ashkenazi Jewish	0.00	0.00
East Asian	0.000331	0.000326
Finnish	0.000193	0.000185
European (Non-Finnish)	0.000483	0.000466
Middle Eastern	0.000331	0.000326
South Asian	0.000307	0.000261
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Heme-dependent dioxygenase that catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L- tryptophan to N-formyl-L-kynurenine. Catalyzes the oxidative cleavage of the indole moiety. {ECO:0000255|HAMAP-Rule:MF_03020, ECO:0000269|PubMed:25066423, ECO:0000269|PubMed:27762317, ECO:0000269|PubMed:28285122}.
• Disease: DISEASE: Hypertryptophanemia (HYPTRP) [MIM:600627]: An autosomal recessive condition characterized by persistent hypertryptophanemia and hyperserotoninemia. {ECO:0000269|PubMed:28285122}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tryptophan metabolism - Homo sapiens (human);Tryptophan Metabolism;NAD Biosynthesis II (from tryptophan);NAD+ biosynthetic pathways;Amino Acid metabolism;Tryptophan metabolism;Monoamine Transport;Tryptophan catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde;Metabolism;L-kynurenine degradation;NAD <i>de novo</i> biosynthesis;Tryptophan degradation;superpathway of tryptophan utilization;tryptophan degradation (Consensus)

Recessive Scores

• pRec: 0.359

Intolerance Scores

• loftool: 0.387
• rvis_EVS: 0
• rvis_percentile_EVS: 53.73

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.754

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: tryptophan catabolic process;tryptophan catabolic process to kynurenine;tryptophan catabolic process to acetyl-CoA;protein homotetramerization;oxidation-reduction process;response to nitroglycerin
• Cellular component: cytosol
• Molecular function: tryptophan 2,3-dioxygenase activity;protein binding;amino acid binding;oxygen binding;heme binding;identical protein binding;metal ion binding